Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils.

Mild modification of intravenous immunoglobulin (IVIG) has been reported to result in enhanced polyspecificity and leveraged therapeutic effects in animal models of inflammation. Here, we observed that IVIG modification by ferrous ions, heme or low pH exposure, shifted the repertoires of specificities in different directions. Ferrous ions exposed Fe(II)-IVIG, but not heme or low pH exposed IVIG, showed increased pro-apoptotic effects on neutrophil granulocytes that relied on a FAS-dependent mechanism. These effects were also observed in human neutrophils primed by inflammatory mediators or rheumatoid arthritis joint fluid in vitro, or patient neutrophils ex vivo from acute Crohn's disease. These observations indicate that IVIG-mediated effects on cells can be enhanced by IVIG modification, yet specific modification conditions may be required to target specific molecular pathways and eventually to enhance the therapeutic potential

Effect of dairy consumption on cognition in older adults: A population-based cohort study.

OBJECTIVE We aimed to assess the effect on cognitive function of adding dairy (total, fermented, non-fermented, full fat, low fat, and sugary) to the diet and of substituting some food groups for dairy. DESIGN Secondary analysis of a prospective population-based cohort study. PARTICIPANTS We analyzed data from 1334 cognitively healthy participants (median age 67 years at baseline) with a mean follow-up of 5.6 years from the CoLaus|PsyColaus cohort in Lausanne, Switzerland. MEASUREMENTS The participants completed a food frequency questionnaire at baseline and cognitive tests at baseline and at follow-up. Clinical dementia rating was the primary outcome. Subjective cognitive decline, memory, verbal fluency, executive and motor functions were secondary outcomes. METHODS Our exposure was the consumption of total and 5 sub-types of dairy products (g/d). We used marginal structural models to compute average causal effects of 1) increasing dairy consumption by 100 g/d and 2) substituting 100 g/d of meat, fish, eggs, fruits and vegetables with dairy on the outcomes. We used inverse probability of the treatment and lost to follow-up weighting to account for measured confounding and non-random loss to follow-up. RESULTS Overall, the effects of adding dairy products to the diet on cognition were negligible and imprecise. No substitution had a substantial and consistent effect on clinical dementia rating. The substitution of fish [11.7% (-3% to 26.5%)] and eggs [18% (2.3%-33.7%)] for dairy products could negatively impact verbal memory and neurolinguistic processes. CONCLUSION We found no effect of adding dairy to the diet or substituting meat, vegetables or fruit for dairy on cognitive function in this cohort of older adults. The substitution of fish and eggs for dairy could have a negative effect on some secondary outcomes, but more studies modeling food substitutions are needed to confirm these results

Board examination for anatomical pathology in Switzerland: two intense days to verify professional competence

About 15years ago, the Swiss Society of Pathology has developed and implemented a board examination in anatomical pathology. We describe herein the contents covered by this 2-day exam (autopsy pathology, cytology, histopathology, molecular pathology, and basic knowledge about mechanisms of disease) and its exact modalities, sketch a brief history of the exam, and finish with a concise discussion about the possible objectives and putative benefits weighed against the hardship that it imposes on the candidate

Alignment of the CMS tracker with LHC and cosmic ray data

© CERN 2014 for the benefit of the CMS collaboration, published under the terms of the Creative Commons Attribution 3.0 License by IOP Publishing Ltd and Sissa Medialab srl. Any further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation and DOI.The central component of the CMS detector is the largest silicon tracker ever built. The precise alignment of this complex device is a formidable challenge, and only achievable with a significant extension of the technologies routinely used for tracking detectors in the past. This article describes the full-scale alignment procedure as it is used during LHC operations. Among the specific features of the method are the simultaneous determination of up to 200 000 alignment parameters with tracks, the measurement of individual sensor curvature parameters, the control of systematic misalignment effects, and the implementation of the whole procedure in a multi-processor environment for high execution speed. Overall, the achieved statistical accuracy on the module alignment is found to be significantly better than 10μm

Oxidation of Antibacterial Compounds by Ozone and Hydroxyl Radical: Elimination of Biological Activity during Aqueous Ozonation Processes

A wide variety of antibacterial compounds is rapidly oxidized by O-3 and hydroxyl radical ((OH)-O-center dot) during aqueous ozonation. Quantitative microbiological assays have been developed here or adapted from existing methods and utilized to measure the resulting changes in antibacterial potencies during O-3 and (OH)-O-center dot treatment of 13 antibacterial molecules (roxithromycin, azithromycin, tylosin, ciprofloxacin, enrofloxacin, penicillin G, cephalexin, sulfamethoxazole,trimethoprim, lincomycin, tetracycline, vancomycin, and amikacin) from 9 structural classes (macrolides, fluoroquinolones, beta-lactams, sulfonamides, dihydrofolate reductase inhibitors, lincosamides, tetracyclines, glycopeptides, and aminoglycosides), as well as the biocide triclosan. Potency measurements were determined from dose-response relationships obtained by exposing Escherichia coli or Bacillus subtilis reference strains to treated samples of each antibacterial compound via broth micro- or macrodilution assays and related to the measured residual concentrations of parent antibacterial in each sample. Data obtained from these experiments show that O-3 and (OH)-O-center dot reactions lead in nearly all cases to stoichiometric elimination of antibacterial activity (i.e., loss of 1 mole equivalent of potency per mole of parent compound consumed). The beta-lactams penicillin G (PG) and cephalexin (CP) represent the only clear exceptions, as bioassay measurements indicate that biologically active products may be formed in the reactions of these two compounds with both O-3 and (OH)-O-center dot. The active product(s) generated in the direct reaction of O-3 with PG appear(s) to be recalcitrant to further transformation by O-3, though any biologically active products formed in the reactions of CP with O-3, or of either PG or CP with (OH)-O-center dot, are apparently deactivated by further reactions with O-3 or (OH)-O-center dot, respectively. Thus, with few exceptions, it can be expected that municipal wastewater ozonation will generally yield sufficient structural modification of antibacterial molecules to eliminate their antibacterial activities, whether oxidation results from selective reactions with O-3 or from relatively nonselective reactions with incidentally produced (OH)-O-center dot

Column studies to assess the effects of climate variables on redox processes during riverbank filtration

Riverbank filtration is an established technique used world-wide to produce clean drinking water in a reliable and cost-efficient way. This practice is, however, facing new challenges posed by climate change, as already observed during past heat waves with the local occurrence of anoxic conditions. In this study we investigated the effect of direct (temperature) and indirect (dissolved organic matter (DOM) concentration and composition, flow rate) climate change variables on redox processes (aerobic respiration, denitrification and Mn(III/IV)/Fe(III) reduction) by means of column experiments. Natural river water, modified river water and river water mixed with treated wastewater effluent were used as feed waters for the columns filled with natural sand from a river-infiltration system in Switzerland. Biodegradable dissolved organic matter was mainly removed immediately at the column inlet and particulate organic matter (POM) associated with the natural sand was the main electron donor for aerobic respiration throughout the column. Low infiltration rates (<= 0.01 m/h) enhanced the oxygen consumption leading to anoxic conditions. DOM consumption did not seem to be sensitive to temperature, although oxygen consumption (i.e., associated with POM degradation) showed a strong temperature dependence with an activation energy of similar to 70 kJmol(-1). Anoxic conditions developed at 30 degrees C with partial denitrification and formation of nitrite and ammonium. In absence of oxygen and nitrate, Mn(II) was mobilized at 20 degrees C, highlighting the importance of nitrate acting as a redox buffer under anoxic conditions preventing the reductive dissolution of Mn(III/IV)(hydr)oxides. Reductive dissolution of Fe(III)(hydr)oxides was not observed under these conditions. (C) 2014 Elsevier Ltd. All lights reserved

Mechanistic and kinetic evaluation of organic disinfection by-product and assimilable organic carbon (AOC) formation during the ozonation of drinking water

Ozonation of drinking water results in the formation of low molecular weight (LMW) organic by-products. These compounds are easily utilisable by microorganisms and can result in biological instability of the water. In this study, we have combined a novel bioassay for assessment of assimilable organic carbon (AOC) with the detection of selected organic acids, aldehydes and ketones to study organic by-product formation during ozonation. We have investigated the kinetic evolution of LMW compounds as a function of ozone exposure. A substantial fraction of the organic compounds formed immediately upon exposure to ozone and organic acids comprised 60-80% of the newly formed AOC. Based on experiments performed with and without hydroxyl radical scavengers, we concluded that direct ozone reactions were mainly responsible for the formation of small organic compounds. It was also demonstrated that the laboratory-scale experiments are adequate models to describe the formation of LMW organic compounds during ozonation in full-scale treatment of surface water. Thus, the kinetic and mechanistic information gained during the laboratory-scale experiments can be utilised for upscaling to full-scale water treatment plants. (c) 2006 Elsevier Ltd. All rights reserved

Transformation of beta-Lactam Antibacterial Agents during Aqueous Ozonation: Reaction Pathways and Quantitative Bioassay of Biologically-Active Oxidation Products

Reactions of ozone (O-3) with the beta-lactam antibiotics penicillin G (PG) and cephalexin (CP) have previously been found to yield products retaining antibacterial activities. These products are unequivocally identified here as the stereoisomeric (R)-sulfoxides of each parent molecule and characterized by a combination of chemical analysis and an antibacterial activity assay. PG-(R)-sulfoxide, which is similar to 15% as potent as PG itself, is formed in similar to 55% yield, whereas CP-(R)-sulfoxide, which is similar to 83% as active as CP, is formed with a maximum similar to 34% yield. PG-(R)-sulfoxide is recalcitrant toward further oxidation by O-3, but readily transformed by hydroxyl radical (HO center dot) k(HO center dot)(,app)(N) = 7.4 x 10(9) M(-1)s(-1), pH 7), resulting in quantitative elimination of its antibacterial activity. In contrast CP-(R)-sulfoxide is degraded by both O-3 and HO center dot (k"(O3,app) = 2.6 x 10(4) M-1 s(-1) and k"(HO center dot,app) = 7.6 x 10(9) M-1 s(-1), pH 7), leading to quantitative elimination of its antibacterial activity. During ozonation of a secondary municipal wastewater effluent sample (pH 8.1, C-DOC = 4.0 mg/L, [alkalinity] = 3.6 mM as HCO3-) spiked with [PG](0) = 1 mu M, PG-(R)-sulfoxide yields did not exceed 0.15 mu M for O-3 doses up to 100 mu M (4.8 mg/L), but reached 0.47 mu M with 10-mM t-BuOH added as a HO center dot scavenger. In contrast, CP-(R)-sulfoxide yields did not exceed 0.1 mu M for the same wastewater spiked with [CP](0) = 1,mu M in either the presence or absence of t-BuOH, indicating that CP-(R)-sulfoxide transformation is governed primarily by direct reaction with O-3. These findings suggest that, for a given degree of parent compound transformation, PG-(R)-sulfoxide yields would likely be greatest during zonation of wastewaters characterized by low O-3 demands and high HO center dot scavenging rates, whereas CP-(R)-sulfoxide yields would be less matrix-dependent In general, complete deactivation of penicillins during wastewater treatment will likely require higher O-3 exposures than necessary for deactivation of cephalosporins